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A DNA delivery system containing listeriolys in Oresults in enhanced hepatocytedirected gene expression

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World Journal of Gastroenterology 1999年第6期5卷 465-469页

作者： Cherie M. Walton, catherine h. wu and George Y. wu Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT United States Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT 06030 United States

AIM To determine whether incorporation of the ph dependent bacterial toxin listeriolysin O (LLO) into the DNA carrier system could increase the endosomal escape of internalized DNA and result gene expression. METhODS A multi component delivery system was prepared consisting of asialoglycoprotein (ASG), poly L lysine (PL), and LLO. Two marker genes, luciferase and β galactosidase in plasmids were complexed and administered in vitro to huh7[ASG receptor (+) ] and SK hep1[ASG receptor (-) ] cells. Purity, hemolytic activity, gene expression, specificity, and toxicity were evaluated. RESULTS An LLO containing conjugate retained cell targeting specificity and membranolytic activity. In ASG receptor (+) cells, luciferase gene expression was enhanced by more than 7 fold over that of conjugates without the incorporation of listeriolysin O. No significant expression occurred in ASG receptor (-) cells. Enhancement of β galactosidase gene expression was less, but still significantly increased over controls. There was no detectable toxicity at concentrations shown to be effective in transfection studies. CONCLUSIONS ASOR PL can be coupled to LLO using disulfide bonds, and successfully target and increase the gene expression of foreign DNA.

关键词： DNA gene expression listeriolysin O hepatocytes

Inhibition of hepatitis C virus replication by single-stranded RNA structural mimics

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World Journal of Gastroenterology 2010年第17期16卷 2100-2108页

作者： Robert Smolic Martina Smolic John h Andorfer catherine h wu Robert M Smith George Y wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health Center263 Farmington Ave.FarmingtonCT 06030-1845United States

AIM: To examine the effect of hepatitis C virus (hCV) structural mimics of regulatory regions of the genome on hCV ***: hCV RNA structural mimics were constructed and tested in a hCV genotype 1b aBB7 replicon,and a Japanese fulminant hepatitis-1 (JFh-1) hCV genotype 2a infection *** sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral ***7.5 cells bearing the BB7 replicon or infected with JFh-1 virus were transfected with expression vectors generating hCV mimics and *** hCV RNA and protein levels were quantified by real-time polymerase chain reaction and Western blotting,*** evaluate possible antisense effects,complementary RNAs spanning a mimic were ***: In the BB7 genotype 1b replicon system,mimics of the polymerase (NS-5B),X and BA regions inhibited replication by more than 90%,50%,and 60%,*** the JFh-1 genotype 2 infection system,mimics that were only 74% and 46% identical in sequence relative to the corresponding region in JFh-1 inhibited hCV replication by 91.5% and 91.2%,respectively,as effectively as a mimic with complete identity to hCV genotype *** inhibitory effects were confirmed by NS3 protein *** RNA molecules spanning the 74% identical mimic had no significant ***: hCV RNA structural mimics can inhibit hCV RNA replication in replicon and infectious hCV systems and do so independent of close sequence identity with the target.

关键词： hepatitis C virus Japanese fulminant hepatitis virus Complementarity RNA sequence hybridization

The immune response to SARS-CoV-2 in people with hIV

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Cellular & Molecular Immunology 2024年第2期21卷 184-196页

作者： Maxine A.höft Wendy A.Burgers catherine Riou Institute of Infectious Disease and Molecular Medicine University of Cape TownCape TownSouth Africa Division of Medical Virology Department of PathologyUniversity of Cape TownCape TownSouth Africa Wellcome Centre for Infectious Diseases Research in Africa University of Cape TownCape TownSouth Africa

This review examines the intersection of the hIV and SARS-CoV-2 *** with hIV(PWh)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral *** COVID-19 in those with wellcontrolled hIV infection poses no greater risk than that for hIV-uninfected individuals,people with advanced hIV disease are more vulnerable to poor COVID-19 ***-19 vaccines are effective and well tolerated in the majority of PWh,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in *** is likely a result of suboptimal humoral and cellular immune responses after *** with advanced hIV may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent ***-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWh who are moderately to severely *** recommend continued research and monitoring of PWh with SARS-CoV-2 infection,especially in areas with a high hIV burden.

关键词： SARS-CoV-2 hIV Immune dysfunction Vaccine efficacy Prolonged infection Immunogenicity

An Improved Method for Preparation of Uniform and Functional Mitochondria from Fresh Liver

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Journal of Clinical and Translational hepatology 2019年第1期7卷 46-50页

作者： Nagham Khouri Farah Xiaocong Liu catherine h.wu George Y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Background and Aims:As the major energy source for mammalian cells,mitochondria have been the subject of numerous ***,the isolation and purification of healthy mitochondria,especially from fresh tissue,remains *** most popular methods and kits involve various centrifugation steps which require substantial time and equipment but do not consistently provide pure preparations of functional *** aim of this study was to determine whether methods could be devised to improve the purity and yield of functional mitochondria from fresh ***:Fresh mouse liver was homogenized,and cells *** size analysis,quantitation of mitochondrial DNA,mitochondrial oxygen consumption,and purity of mitochondria(by electron microscopy)were measured in samples after various purification steps and significant differences ***:A two-step procedure consisting of centrifugation followed by filtration through 1.2μand 0.8μfilters resulted in uniform mitochondrial preparations with diameters between 520-540 nm,and approximately 5-times more pure *** mitochondria thus obtained had oxygen consumption and sensitivities to mitochondrial inhibitors that were indistinguishable from those purified by centrifugation *** microscopy confirmed the presence of more uniform and 4-5 times greater concentrations of mitochondria compared to centrifugation ***:A two-step procedure consisting of sequential centrifugation followed by filtration is a rapid method for the production of highly purified,uniform and functional mitochondria.

关键词： Mitochondria Isolation Filtration Purified Uniform Functional

Secondary Structural Elements of the hCV X-region Involved in Viral Replication

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Journal of Clinical and Translational hepatology 2015年第1期3卷 1-8页

作者： Nidhi Gupta catherine h.wu George Y.wu Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Background and Aims:The noncoding regions in the 3'-untranslated region (UTR) of the hepatitis C virus (hCV)genome contain secondary structures that are important for *** aim of this study was to identify detailed conformational elements of the X-region involved in hCV ***:Ribonucleic acid (RNA) structural analogs X94,X12,and X12c were constructed to have identical conformation but 94%,12%,and 0% sequence identity,respectively,to the X region of hCV genotype *** of structural analogs on replication of hCV genotypes 1b and 2a hCV RNA were studied by quantitative reverse transcriptase polymerase chain ***:In replicon BB7 cells,a constitutive replication model,hCV RNA levels decreased to 55%,52%,53%,and 54% after transfection with expression plasmids generating RNA structural analogs 5B-46,X-94,X-12,and X-12c,respectively (phCV genotype 2a infection model,RNA analogs 5B-46,X-94,and X-12 in hepatic cells inhibited replication to 11%,9%,and 12%,*** the X-12 analog was only 12% identical to the corresponding sequence of hCV genotype 2a,the sequence per se,or antisense effects were unlikely to be ***:The data suggest that conformation of secondary structures in 3'-UTR of hCV RNA genome is required for hCV *** expression of RNA analogs predicted to have identical stem-loop structures might inhibit hCV infection of hepatocytes in liver and may represent a novel approach to design anti-hCV agents.

关键词： hCV RNA genome hCV X-region hepatitis C virus Infection Japanese Fulminant hepatitis Virus RNA secondary structure

Convexification of hybrid AC-DC Optimal Power Flow with Line-Commutated Converters

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 617-628页

作者： hongyuan Liang Zhigang Li J.h.Zheng Q.h.wu School of Electric Power Engineering South China University of TechnologyGuangzhou 510641China

Line-commutated converter (LCC)-based high-voltage DC (hVDC) systems have been integrated with bulk AC power grids for interregional transmission of renewable power. The nonlinear LCC model brings additional nonconvexity to optimal power flow (OPF) of hybrid AC-DC power grids. A convexification method for the LCC station model could address such nonconvexity but has rarely been discussed. We devise an equivalent reformulation for classical LCC station models that facilitates second-order cone convex relaxation for the OPF of LCC-based AC-DC power grids. We also propose sufficient conditions for exactness of convex relaxation with its proof. Equivalence of the proposed LCC station models and properties, exactness, and effectiveness of convex relaxation are verified using four numerical simulations. Simulation results demonstrate a globally optimal solution of the original OPF can be efficiently obtained from relaxed model.

关键词： AC-DC power system convex relaxation linecommutated converter optimal power flow second-order cone programming

A hybrid Signal Processing Method Combining Mathematical Morphology and Walsh Theory for Power Quality Disturbance Detection and Classification

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 584-592页

作者： Zhi Ding Tianyao Ji Mengshi Li Q.h.wu School of Electric Power Engineering South China University of Technology(SCUT)Guangzhou 510641China

In this paper, a novel signal processing method combining mathematical morphology (MM) and Walsh theory is proposed, which uses Walsh functions to control the structuring element (SE) and MM operators. Based on the Walsh-MM method, a scheme for power quality disturbances detection and classification is developed, which involves three steps: denoising, feature extraction and morphological clustering. First, various evolution rules of Walsh function are used to generate groups of SEs for the multiscale Walsh-ordered morphological operation, so the original signal can be denoised. Next, the fundamental wave of the denoised signal is suppressed by hadamard matrix;thus, disturbances can be extracted. Finally, the Walsh power spectrum of the waveform extracted in the previous step is calculated, and the parameters of which are taken by morphological clustering to classify the disturbances. Simulation results reveal the proposed scheme can effectively detect and classify disturbances, and the Walsh-MM method is less affected by noise and only involves simple calculation, which has a potential to be implemented in hardware and more suitable for real-time application.

关键词： hadamard matrix mathematical morphology morphological clustering power quality disturbance Walsh theory

Location of Asymmetric Ground Fault Using Virtual Injected Current Ratio and Two-stage Recovery Strategy in Distribution Networks

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CSEE Journal of Power and Energy Systems 2024年第1期10卷 151-161页

作者： haiting Shan Luliang Zhang Q.h.wu Mengshi Li School of Electric Power Engineering South China University of Technology(SCUT)Guangzhou 510641China

Sparse measurements challenge fault location in distribution *** paper proposes a method for asymmetric ground fault location in distribution networks with limited measurements.A virtual injected current vector is formulated to estimate the fault line,which can be reconstructed from voltage sags measured at a few buses using compressive sensing(CS).The relationship between the virtual injected current ratio(VICR)and fault position is deduced from circuit analysis to pinpoint the ***,a two-stage recovery strategy is proposed for improving reconstruction accuracy of the current vector,where two different sensing matrixes are utilized to improve the *** proposed method is validated in IEEE 34 node test *** results show asymmetric ground fault type,resistance,fault position and access of distributed generators(DGs)do not significantly influence performance of our *** addition,it works effectively under various scenarios of noisy measurement and line parameter *** on 134 node test feeders prove the proposed method is also suitable for systems with more complex structure.

关键词： Distribution networks fault location reconstruction accuracy two-stage recovery virtual injected current ratio

Observability Analysis of Integrated Electricity and heating Systems with Thermal Quasi-dynamics in Pipelines

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 1145-1158页

作者： Zhigang Li Wenjian Zheng Junbo Zhao J.h.Zheng Q.h.wu School of Electric Power Engineering South China University of TechnologyGuangzhou 510641China Fuzhou Changle District Power Supply Company of State Grid Fujian Electric Power Co. Ltd.Fuzhou 350000China Department of Electrical and Computer Engineering University of ConnecticutStorrsCT 06269USA CSEE IEEE

Observability analysis(OA)is vital to obtaining the available input measurements of state estimation(SE)in an integrated electricity and heating system(IEhS).Considering the thermal quasi-dynamics in pipelines,the measurement equations in heating systems are dependent on the estimated results,leading to an interdependency between OA and *** OA methods require measurement equations be known exactly before SE is performed,and they are not applicable to *** bridge this gap,a scenario-based OA scheme for IEhSs is devised that yields reliable analysis results for a predefined set of time-delay scenarios to cope with this *** its core procedure,the observable state identification and observability restoration are formulated in terms of integer linear *** tests are conducted to demonstrate the validity and superiority of the proposed formulation.

关键词： Integrated electricity and heating system measurement observability analysis state estimation thermal quasi-dynamics